The effects of age at the onset of drinking to intoxication and chronic ethanol self-administration in male rhesus macaques

Helms, Christa M.; Rau, Andrew R.; Shaw, Jessica K.; Stull, Cara; Gonzales, Steven W.; Grant, Kathleen A.

doi:10.1007/s00213-013-3417-x

Cited by 36 publications

(46 citation statements)

References 40 publications

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“…All procedures were conducted in accordance with the NIH and the Guide for the Care and Use of Laboratory Animals and approved by the Oregon National Primate Research Center IACUC. Data analysis on ethanol self-administration and MRI structural brain imaging from these animals have been published (Helms et al 2014; Kroenke et al 2014). …”

Section: Methodsmentioning

confidence: 99%

Adrenal steroid hormones and ethanol self-administration in male rhesus macaques

2014

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Rationale Hypothalamic-pituitary-adrenal (HPA) axis hormones have neuroactive metabolites with receptor activity similar to ethanol. Objectives The present study related HPA hormones in naïve monkeys to ethanol self-administration. Methods Morning plasma adrenocorticotropic hormone (ACTH), cortisol, deoxycorticosterone (DOC), aldosterone and dehydroepiandrosterone-sulfate (DHEA-S) were measured longitudinally in male rhesus macaques (Macaca mulatta) induced to drink ethanol followed by access to ethanol (4% w/v, in water) and water 22 hours/day for 12 months. Results During ethanol access, DOC increased among non-heavy (average intake over 12 months ≤ 3.0 g/kg/day, n = 23) but not heavy drinkers (> 3.0 g/kg/day, n = 9), aldosterone was greater among heavy drinkers after 6 months. The ratio of DOC/aldosterone decreased only among heavy drinkers after 6 or12 months of ethanol self-administration. ACTH only correlated significantly with DHEA-S, the ratio of cortisol/DHEA-S and DOC after the onset of ethanol access, the former two just in heavy drinkers. Baseline hormones did not predict subsequent ethanol intake over 12 months, but baseline DOC correlated with average blood-ethanol concentrations (BEC), among all monkeys and heavy drinkers as a group. During ethanol access, aldosterone and DOC correlated and tended to correlate, respectively, with 12-month average ethanol intake. Conclusions Ethanol self-administration lowered ACTH and selectively altered its adrenocortical regulation. Mineralocorticoids may compensate for adrenocortical adaptation among heavy drinkers and balance fluid homeostasis. As DOC was uniquely predictive of future BEC) and not water intake, to the exclusion of aldosterone, GABAergic neuroactive metabolites of DOC may be risk factors for binge drinking to intoxication.

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Section: Methodsmentioning

confidence: 99%

Adrenal steroid hormones and ethanol self-administration in male rhesus macaques

2014

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“…Because ethanol intake did not appear to modulate sEPSC amplitude, our results suggest that age of onset of ethanol drinking is not likely a risk factor for the development of aberrant synaptic function in the BNST. Interestingly, we have previously shown that age of onset is a risk factor for heavy drinking in this translational model (Helms et al, 2014b), suggesting that alterations in excitatory synaptic transmission in the BNST are more likely related to the consequences, rather than the risk, of chronic ethanol consumption.…”

Section: Discussionmentioning

confidence: 78%

Effects of chronic alcohol consumption on neuronal function in the non-human primate BNST

et al. 2015

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Alterations in hypothalamic-pituitary-adrenal (HPA) axis function contribute to many of the adverse behavioral effects of chronic voluntary alcohol drinking, including alcohol dependence and mood disorders; limbic brain structures such as the bed nucleus of the stria terminalis (BNST) may be key sites for these effects. Here, we measured circulating levels of several steroid hormones and performed whole-cell electrophysiological recordings from acutely-prepared BNST slices of male rhesus monkeys allowed to self-administer alcohol for 12 months or a control solution. Initial comparisons revealed that BNST neurons in alcohol-drinking monkeys had decreased membrane resistance, increased frequency of spontaneous inhibitory postsynaptic currents (sIPSCs) with no change in spontaneous excitatory postsynaptic currents (sEPSCs). We then used a combined variable cluster analysis and linear mixed model statistical approach to determine whether specific factors including stress and sex hormones, age, and measures of alcohol consumption and intoxication are related to these BNST measures. Modeling results showed that specific measures of alcohol consumption and stress-related hormone levels predicted differences in membrane conductance in BNST neurons. Distinct groups of adrenal stress hormones were negatively associated with the frequency of sIPSCs and sEPSCs, and alcohol drinking measures and basal neuronal membrane properties were additional positive predictors of inhibitory, but not excitatory, PSCs. The amplitude of sEPSCs was highly positively correlated with age, independent of other variables. Together, these results suggest that chronic voluntary alcohol consumption strongly influences limbic function in non-human primates, potentially via interactions with or modulation by other physiological variables, including stress steroid hormones and age.

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“…Body weights were recorded weekly throughout the study. Alcohol intake and blood alcohol concentration data for some of these subjects have been published elsewhere [37, 38]. …”

Section: Methodsmentioning

confidence: 99%

Twelve months of voluntary heavy alcohol consumption in male rhesus macaques suppresses intracortical bone remodeling

Gaddini

Grant

Woodall

et al. 2015

Bone

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Chronic heavy alcohol consumption is a risk factor for cortical bone fractures in males. The increase in fracture risk may be due, in part, to reduced bone quality. Intracortical (osteonal) bone remodeling is the principle mechanism for maintaining cortical bone quality. However, it is not clear how alcohol abuse impacts intracortical bone remodeling. This study investigated the effects of long-duration heavy alcohol consumption on intracortical bone remodeling in a non-human primate model. Following a 4-month induction period, male rhesus macaques (Macaca mulatta, n = 21) were allowed to voluntarily self-administer water or alcohol (4% ethanol w/v) for 22 h/d, 7 d/wk for 12 months. Control monkeys (n = 13) received water and an isocaloric maltose-dextrin solution. Tetracycline hydrochloride was administered orally 17 and 3 days prior to sacrifice for determination of active mineralization sites. Animals in the alcohol group consumed 2.7 ± 0.2 g alcohol/kg/d (mean ± SE) during the 12 months of self-administration, resulting in a mean daily blood alcohol concentration of 77 ± 9 mg/dl from samples taken at 7 h after the start of a daily session. However, blood alcohol concentration varied widely from day to day, with peak levels exceeding 250 mg/dl, modeling a binge-drinking pattern of alcohol consumption. The skeletal response to alcohol was determined by densitometry, microcomputed tomography and histomorphometry. Significant differences in tibial bone mineral content, bone mineral density, and cortical bone architecture (cross-sectional volume, cortical volume, marrow volume, cortical thickness, and polar moment of inertia) in the tibial diaphysis were not detected with treatment. However, cortical porosity was lower (1.8 ± 0.5 % versus 0.6 ± 0.1 %, p = 0.021) and labeled osteon density was lower (0.41 ± 0.2/mm2 versus 0.04 ± 0.01/mm2, p < 0.003) in alcohol-consuming monkeys compared to controls, indicating a reduced rate of intracortical bone remodeling. In concordance, plasma CTx was lower (2.5 ± 0.3 ng/ml versus 1.7 ± 0.1 ng/ml, p = 0.028) in the alcohol group. These results suggest that chronic heavy alcohol consumption may negatively impact bone health, in part, by suppressing intracortical bone remodeling.

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The effects of age at the onset of drinking to intoxication and chronic ethanol self-administration in male rhesus macaques

Cited by 36 publications

References 40 publications

Adrenal steroid hormones and ethanol self-administration in male rhesus macaques

Adrenal steroid hormones and ethanol self-administration in male rhesus macaques

Effects of chronic alcohol consumption on neuronal function in the non-human primate BNST

Twelve months of voluntary heavy alcohol consumption in male rhesus macaques suppresses intracortical bone remodeling

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